Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same

Sahu, Vishal; Nigam, Lokesh; Agnihotri, Vertica; Gupta, Abhishek; Shekhar, Shashank; Subbarao, Naidu; Bhaskar, Suman; Dey, Sharmistha

doi:10.4143/crt.2018.105

Cited by 18 publications

(21 citation statements)

References 15 publications

(15 reference statements)

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“…Perineural invasion and lymphovascular invasion were widely investigative predictors for poor prognosis in oral SCC patients, strongly correlating with tumor site, tumor stage, and disease stage [26,27]. It was noted perineural invasion and lymphovascular invasion were more frequent in NPC survivors, the finding was a little out of our expectation.…”

Section: Discussionmentioning

confidence: 85%

Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma

Dai

Fang

et al. 2020

Cancer Res Treat

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The main goal of this study was to analyze the prognosis of secondary oral squamous cell carcinoma (SCC) with a comparison with sporadic oral SCC by a matched-pair design. Materials and Methods Records of patients with surgically treated primary oral SCC were reviewed, and a total of 83 patients with previous history of radiotherapy for nasopharyngeal carcinoma (NPC) were retrospectively enrolled. A matched-pair study was performed, each NPC survivor was matched with two sporadic oral SCC patients by age, sex, primary tumor site, adverse pathologic characteristics, disease stage, neck node status, and tumor stage. The overall survival (OS) and disease-specific survival (DSS) rates were calculated by the Kaplan-Meier method; independent prognostic factors were evaluated by the Cox proportional hazards method. Results Compared with sporadic oral SCC patients, NPC survivors were less likely to be smokers (p=0.004), perineural invasion and lymphovascular invasion were more common in NPC survivors (both p < 0.001). The 5-year OS and DSS rates in NPC survivors were 47% and 54%, respectively; the 5-year OS and DSS rates in sporadic oral SCC patients were 62% and 67%, respectively; the difference was significant (both p < 0.05). In survival analysis, disease stage remained to be independent prognostic factor for both the OS and DSS. Conclusion NPC survivors had worse OS and DSS than sporadic oral SCC patients, NPC survivors were less likely to be smokers, but had higher opportunity of perineural invasion and lymphovascular invasion. Disease stage was the most important predictor for the survival in NPC survivors.

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Section: Discussionmentioning

confidence: 85%

Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma

Dai

Fang

et al. 2020

Cancer Res Treat

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“…To the best of our knowledge, very few studies measured serum levels of MKP-1 and p-p38 when investigating their roles in the development of a specific disease, since they are intracellular signalling proteins. But serum MKP-1 and p38 levels were really detected by ELISA in some studies [34,35], Our study showed that the difference of serum MKP-1 levels between AIH and healthy people AIH was also significant. By blocking Tim-3, p38 was activated and MKP-1 was inhibited, thus upregulating IL-17A expression and promoting the development of AIH.…”

Section: Discussionmentioning

confidence: 63%

Tim‐3 suppresses autoimmune hepatitis via the p38/MKP‐1 pathway in Th17 cells

Tang

Zhou

et al. 2021

FEBS Open Bio

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T cell immunoglobulin-and mucin-domain-containing molecule-3 (Tim-3) mediates T cell suppression in various autoimmune diseases, such as chronic inflammatory liver disease. However, the regulatory effect of Tim-3 on Th17 cells in AIH (autoimmune hepatitis) is incompletely understood. Here, we studied the expression and function of Tim-3 in T cells in AIH patients and in a Con A (Concanavalin A)-induced mouse AIH model. We report that the frequency of CD4 + Tim-3 + T cells in peripheral blood samples of AIH patients was lower than that in the control group. The p38/MKP-1 and p-JNK pathways were activated and the expression of interleukin-17A protein was elevated in patients with AIH. Furthermore, the extent of pathological damage in the livers of mice with a blocked Tim-3 signaling pathway (anti-Tim-3 group) was markedly increased and correlated with elevated ALT and AST levels. In addition, the frequency of CD4 + IL-17 + T (Th17) cells in the anti-Tim-3 group was increased, while that in mice with blocked p38 activity was decreased. Finally, expression of MKP-1 (p-p38) gradually increased in the control, Con A, and anti-Tim-3 groups, but the levels of interleukin-17A were decreased in the p38-blocked group. In summary, our results suggest that Tim-3 suppresses AIH by regulating Th17 cells through the p38/MKP-1 pathway.

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“…Furthermore, p38 can both sensitize some tumor types to chemotherapy and facilitates resistance in others, where p38 inhibition may be beneficial in therapeutic approaches [ 136 , 176 , 177 , 178 ]. Of note, p38 MAPK activity and increased expression have been linked to the progression of breast cancer, prostate cancer, bladder cancer, liver cancer, lung cancer, thyroid cancers, leukemia, and many more [ 35 , 135 , 179 , 180 ]. In solid tumor biology, the p38 MAPK pathway has been shown to promote tumor cell survival and angiogenesis during periods of hypoxia, reoxygenation, and nutrient deficiency by inducing expression of metalloproteinases and vascular endothelial growth factor A (VEGFA) [ 135 ].…”

Section: Pathophysiological Implications Of Mkk3/6-dependent P38 Mapksmentioning

confidence: 99%

Atypical p38 Signaling, Activation, and Implications for Disease

Burton

Antoniades

Okáľová

et al. 2021

IJMS

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The mitogen-activated protein kinase (MAPK) p38 is an essential family of kinases, regulating responses to environmental stress and inflammation. There is an ever-increasing plethora of physiological and pathophysiological conditions attributed to p38 activity, ranging from cell division and embryonic development to the control of a multitude of diseases including retinal, cardiovascular, and neurodegenerative diseases, diabetes, and cancer. Despite the decades of intense investigation, a viable therapeutic approach to disrupt p38 signaling remains elusive. A growing body of evidence supports the pathological significance of an understudied atypical p38 signaling pathway. Atypical p38 signaling is driven by a direct interaction between the adaptor protein TAB1 and p38α, driving p38 autophosphorylation independent from the classical MKK3 and MKK6 pathways. Unlike the classical MKK3/6 signaling pathway, atypical signaling is selective for just p38α, and at present has only been characterized during pathophysiological stimulation. Recent studies have linked atypical signaling to dermal and vascular inflammation, myocardial ischemia, cancer metastasis, diabetes, complications during pregnancy, and bacterial and viral infections. Additional studies are required to fully understand how, when, where, and why atypical p38 signaling is induced. Furthermore, the development of selective TAB1-p38 inhibitors represents an exciting new opportunity to selectively inhibit pathological p38 signaling in a wide array of diseases.

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Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same

Abstract: In this study, first time estimated the levels of p38 MAPK isoforms in the serum of HNSCC. It can be concluded that p38 MAPK isoforms can be a diagnostic and prognostic marker for HNSCC and p38δ as a therapeutic target.

Cited by 18 publications

References 15 publications

Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma

Secondary Squamous Cell Carcinoma of the Oral Cavity after Nasopharyngeal Carcinoma

Tim‐3 suppresses autoimmune hepatitis via the p38/MKP‐1 pathway in Th17 cells

Atypical p38 Signaling, Activation, and Implications for Disease

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